**2. Type 2 diabetes (T2D)**

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

indicates significant insulin resistance [5–7].

ing of never being able to eat freely.

of lean mass, and weight loss [12–13].

16 hours of fasting and 8 hours for eating.

IR can be measured by using the homeostatic model assessment of insulin resistance (HOMA-IR) equation. HOMA-IR can be evaluated by fasting glucose and insulin levels. People with T2D commonly have High HOMA-IR score, which

As little as 3% weight reduction produces clinically significant effects to reduce HOMA-IR [8, 9]. The most widely prescribed strategy to induce weight loss is to reduce the daily calory intake [10]. Current guidelines recommended continuous energy restriction (CER) along with comprehensive lifestyle intervention, as the cornerstone of obesity treatment [11]. For some individuals CER are effective for weight loss. However, many people realize that this type of diet is difficult to follow, as it requires robust calorie counting, and frustration is caused be owing to the feel-

There has been increased interest in identifying alternative dietary weight loss strategies, because of the relative ineffectiveness of traditional CER approaches for achieving and sustaining weight loss. One such approach is intermittent fasting (IF) also called intermittent energy restriction (IER) which encompasses various diets that cycle between periods of fasting and no fasting, these diets do not necessarily specify what to eat. The regimens of IER may be easier to follow and maintain over time than CER. Furthermore, people do not fully compensate during fed periods for the lack of energy created during prolonged periods of fasting. Therefore, IER may lead to metabolic adjustments that prefer greater fat mass loss, better maintaining

The IER regimens range from fasting the whole days at a time to fasting for several hours during the day. IER paradigms involve recurring periods with little or no energy intake with intervening periods of ad libitum food intake. The two most popular forms of IER are: the 5: 2 diet characterized by two consecutive or non-consecutive "fast" days and the alternate-day energy restriction, commonly called alternate-day fasting (ADF). The second form is time-restricted feeding (TRF), eating within specific time frames such as the most prevalent 16: 8 diet, with

Previous studies and systematic reviews provide an overview of IER regimes [14–34]. Those studies report the health benefits leading by IER regimes and discuss the physiological mechanisms by which health outcomes might be improved [35]. However, the question of whether IER is always able to reduce HOMA-IR is not answered by the latter studies; In other words, what are the conditions (age, gender, basal fasting glucose level, etc.) needed to make the IER effective for reducing HOMA-IR have not yet been deciphered. Moreover, results of previous studies are

In today's era of precision medicine, we can be motivated to answer the question Can we predict who will be Successful on an IMF or TRF Diet or CER? For example, a patient with prediabetes or diabetes comes to see his physician to ask for advice. Could such patient benefit from a specific IF intervention? Benefit in terms of reducing HOMA-IR or even eliminating the T2D altogether. A recommendation system which suggest effective IF intervention for a certain patient is found in a new study [36]. The recommendation system is based on individual data from human fasting intervention studies. The system presented in the study, predicts which type of IF treatment can improve an individual's health and preventing or curing T2D. A machine learning approach is used to develop the recommendation system while a set of rules which can assist individual patients and their physicians in selecting the

A further question will be discussed in this chapter: Can we predict the optimal intervention IMF or TRF Diet or CER or other for a prediabetes patient? and what is

reported on a group level only rather than report per individual.

best IF intervention is provided by the results of the study.

the accuracy of such prediction?

**388**

Diabetes is a chronic, metabolic disease characterized by elevated levels of blood glucose (or blood sugar). Our metabolism converts food into energy for our bodies to use. One of the things needed for this process is insulin. The pancreas makes a hormone called insulin. The insulin helps the cells turn glucose from the food we eat into energy. After we eat, the sugar levels in our blood rise and insulin is released into the bloodstream. The insulin then makes the cells absorb sugar from the blood. If this process does not work properly, the blood sugar levels rise. The medical term for blood sugar levels that are too high is hyperglycemia.

According to the International Diabetes Federation in 2017 there were 425 million people in the world with diabetes. That is close to 1 in 11 people [37].

#### **2.1 Main types of diabetes**

There are two main types of diabetes: type 1 and type 2. Glucose gives the body cells energy, but to enter the cells it needs insulin. People with type 1 diabetes do not produce insulin; while people with T2D do not respond to insulin as well as they should. Both types of diabetes can lead to chronically high blood sugar levels. Type 1 diabetes usually develops in childhood or teenage years. This disease is a result of damage to the pancreas that leaves it producing either very little insulin or none. Type 1 diabetes is caused by an autoimmune reaction where the body's defense system attacks the cells that produce insulin. Things are different in T2D, where insulin is made by the pancreas, but the body's cells lose the ability to absorb and use the insulin. In people who have T2D, the pancreas produces enough insulin, but it no longer influences the body's cells. The medical term for this is "insulin resistance" (IR). The pancreas can compensate for this for a while by producing more insulin. But at some point, it can no longer keep up, and then blood sugar levels start to rise. T2D is characterized by (IR), where the body does not fully respond to insulin. In the past, T2D was often referred to as "adult-onset" diabetes because it is commonly diagnosed later in life. T2D is much more common than type 1 diabetes. Among all the people living with diabetes, 90–95% percent have T2D. This chapter focuses on T2D.

#### **2.2 Causes and risk factors**

Usually, a combination of things causes T2D. There are several gene mutations linked to diabetes. Not everyone who carries a mutation will get diabetes. However, many people with diabetes do have one or more of these mutations. Being overweight or obese can cause IR. People with insulin resistance often have a group of conditions commonly called "Metabolic syndrome", including high blood sugar, extra fat around the waist, high blood pressure, high cholesterol and high triglycerides. Another cause can be bad communication between cells. Sometimes, cells send the wrong signals or do not pick up messages correctly. When these problems affect how cells make and use insulin or glucose, a chain reaction can lead to diabetes. Finally, broken beta cells can cause diabetes since if the cells that make insulin send out the wrong amount of insulin at the wrong time, blood sugar is not controlled properly.

Various factors can increase the likelihood of developing T2D. They can be described using 3 categories. The category of risk factors is who you are: age of 45 or older, a family relative with diabetes or ethnicity. The second category is health and medical history: being prediabetes can increase the risk for diabetes, heart and blood vessel disease, high blood pressure, low HDL ("good") cholesterol, high triglycerides, being overweight or obese, Gestational diabetes while you were pregnant and finally depression. The last category of risk factors is the daily habits and lifestyle. Among this category we can find factors such as getting little or no exercise, smoking, stress or sleeping too little or too much.

#### **2.3 Symptoms and complications**

T2D can evolve moderately during several years. Blood sugar levels stay high all the time when T2D is untreated. High blood sugar levels may cause the following symptoms: thirstiness, frequent urination, tiredness and apathy, fulsomeness and dizziness or even lose consciousness. In addition to T2D symptoms there are complications of T2D containing, five times more likely to get heart disease or have a stroke, dialysis, or kidney replacement in case the kidneys are damaged. Furthermore, high blood sugar can damage the small blood vessels in the backs of the eyes and in cases of neglect, it can cause blindness. Digestive disorders, not feeling of the feet and sexual response are considered as T2D complications as well. Lesions cure slower and can become infected when blood does not circulate well. Miscarriage are more likely in women with diabetes. A condition in which breathing stops and starts while you sleep might developed. It is more likely to have hearing problems. Finally, high blood sugar can damage your brain and might put you at higher risk of Alzheimer's disease.

#### **2.4 How does T2D diagnosed?**

Hemoglobin is a protein that transports oxygen to the body cells. It can be found inside red blood cells. In cases of high glucose level in the blood glucose can attach the hemoglobin. Hemoglobin that is attached to glucose is called glycated hemoglobin. T2D diabetes is usually diagnosed using the A1C test. A1C test measures the amount of hemoglobin in the blood that has glucose attached to it.

Red blood cells are constantly dying and regenerating. Their lifespan is approximately three months. Glucose attaches (glycates) to hemoglobin inside the red blood cells, so the record of how much glucose is attached to the hemoglobin also lasts for about three months. Normally, about 6 percent of hemoglobin has glucose attached. If there is too much glucose attached to the hemoglobin cells, the test results will be high A1C. If the amount of Glycated hemoglobin amount is normal, the A1C results will be normal. An A1C level of 6.5 percent or higher on two separate tests means you have diabetes.

The symbol A1C represents a specific type of hemoglobin. The "A" in Hemoglobin A (HgbA) stands for "adult." HgbA can be found in two types HgbA1 and HgbA2. In individuals from six months old about 98% of HgbA is type 1 (HgbA1). Type A1 has subtypes A1A, A1B, A1C, and others. Two-thirds of hemoglobin with glucose attached is type A1C [38]. Therefore, HgbA1C is a good marker for glucose control. Larger amount of hemoglobin will be glycated when more glucose is circulating in the blood.

However, the A1C test results are not always meaningful. For example, when we want to measure A1C difference before and after an intervention that is shorter than three months. The difference of A1C before and after the intervention will not tell us the accurate result because it is an average calculation. In such case we need another test to diagnose the glucose level in blood. Fasting blood glucose test is a blood sample which is taken after an overnight fast. A normal level of fasting glucose is a reading of less than 100 mg/dL (5.6 mmol/L). If the fasting blood glucose is 126 mg/dL (7 mmol/L) or higher, it considered diabetes. Values between 100 to 125 considered prediabetes. T2D is generally characterized by insulin resistance, where the body does not fully respond to insulin.

HOMA-IR stands for Homeostatic Model Assessment of Insulin Resistance. Using HOMA-IR equation insulin resistance can be estimated from fasting glucose

**391**

*Selecting Intermittent Fasting Type to Improve Health in Type 2 Diabetes: A Machine Learning…*

and insulin levels. High score of HOMA-IR indicates a significant Insulin resistance which usually found in people with Diabetes Type 2. An updated HOMA model (HOMA2) was published by Jonathan Levy in 1998. HOMA2 model took account of variations in hepatic and peripheral glucose resistance, increases in the insulin secretion curve for plasma glucose concentrations above 10 mmol/L (180 mg/dL) and the contribution of circulating proinsulin [39]. In 2004, the HOMA2 Calculator [40] was released by Oxford university UK. This provides quick and easy access to the HOMA2 model for researchers who wish to use model-derived estimates of Insulin resistance, rather than linear approximations as provided by HOMA-IR model. There are additional tests to diagnose Diabetes type 2,beside those mentioned here, however those methods will not be discussed

There are two approaches to treat T2D. The first is lifestyle changes and the second is medications. Adopting a healthy lifestyle can help lower the risk of diabetes. Healthy life style contains: lose weight, get active, eat right, avoid highly processed carbs, sugary drinks, and trans and saturated fats, limit red and processed meats, quit smoking and finally work to keep from gaining weight after you quit smoking, so you do not create one problem by solving another. It is possible to reach your target blood sugar levels with diet and exercise alone. However, if changing lifestyle is not enough several medicines exist to treat diabetes. Among the medicine functions are: Lowering the amount of glucose your liver makes and helps your body responding better to the insulin. Helping your body make more insulin, making you more sensitive to insulin. Causing slow digestion and lowering blood sugar levels

In historical periods in the past when food was not always available fasting was sure to happen. Many religious philosophies have practiced fasting for centuries; however, cyclically restricting or reducing calories has recently taken off as a way to lose weight and improve health outcomes. Intermittent fasting (IF) is proposed as an alternative dieting strategy. IF includes cycles of fasting and unrestricted eating periods, which may allow more flexibility and thereby enhance devoutness [41]. Intermittent fasting is generally grouped into two main categories: whole-day fasting and time-restricted feeding. Both categories range in flexibility of time spent fasting. The details of intermittent fasting interventions which participate in the

research described in this chapter are found in the following subsections.

45% low glycemic load carbohydrate and 25% protein) [44].

In a paper from 2011 [42] Michelle Harvie describes a randomized controlled trial to compare the feasibility and effectiveness of intermittent continuous energy (IER) with continuous energy restriction (CER) for weight loss, insulin sensitivity and other metabolic disease risk markers. The CER involved a 25% energy restriction from estimated baseline energy requirements using reported metabolic energy turnovers estimated basal metabolic rate [43] for 7 days per week. The CER group was prescribed a daily 25% restriction based on a Mediterranean-type diet (30% fat, 15% monounsaturated, 7.5% saturated fat, 7.5% polyunsaturated fatty acids,

*DOI: http://dx.doi.org/10.5772/intechopen.95336*

further in this chapter.

**2.5 How is T2D treated?**

**3. Intermittent fasting**

and finally help your kidneys filter out more glucose.

**3.1 Continuous energy restriction (CER)**

*Selecting Intermittent Fasting Type to Improve Health in Type 2 Diabetes: A Machine Learning… DOI: http://dx.doi.org/10.5772/intechopen.95336*

and insulin levels. High score of HOMA-IR indicates a significant Insulin resistance which usually found in people with Diabetes Type 2. An updated HOMA model (HOMA2) was published by Jonathan Levy in 1998. HOMA2 model took account of variations in hepatic and peripheral glucose resistance, increases in the insulin secretion curve for plasma glucose concentrations above 10 mmol/L (180 mg/dL) and the contribution of circulating proinsulin [39]. In 2004, the HOMA2 Calculator [40] was released by Oxford university UK. This provides quick and easy access to the HOMA2 model for researchers who wish to use model-derived estimates of Insulin resistance, rather than linear approximations as provided by HOMA-IR model. There are additional tests to diagnose Diabetes type 2,beside those mentioned here, however those methods will not be discussed further in this chapter.
